An unusual allosteric mobility of the C-terminal helix of a high-affinity alpha(L) integrin I domain variant bound to ICAM-5

作者：Zhang Hongmin; Casasnovas Jose M; Jin Moonsoo; Liu Jin huan; Gahmberg Carl G; Springer Timothy A; Wang Jia huai^*

来源：Molecular Cell, 2008, 31(3): 432-437.

DOI：10.1016/j.molcel.2008.06.022

Integrins are cell surface receptors that transduce signals bidirectionally across the plasma membrane. The key event of integrin signaling is the allosteric regulation between its ligand-binding site and the C-terminal helix (alpha 7) of integrin's inserted (1) domain. A significant axial movement of the alpha 7 helix is associated with the open, active conformation of integrins. We describe the crystal structure of an engineered high-affinity I domain from the integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons. The finding that the a7 helix swings out and inserts into a neighboring I domain in an upside-down orientation in the crystals implies an intrinsically unusual mobility of this helix. This remarkable feature allows the alpha 7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling.

• 出版日期2008-8-8